A cerium-dependent photoenzyme

Access through your institution Buy or subscribe Enzymes efficiently catalyze numerous reactions, but re-engineering them to speed up reactions that are not known in nature is challenging.

Lanthanides, particularly cerium complexes, have previously been used in photocatalytic transformations that proceed via radical species. However, these radical reactions are rarely

stereoselective. In an effort to address this, Klein, Leiss-Maier et al. developed a lanthanide-binding enzyme by adding four glutamates in the center of a computationally designed protein

scaffold. The resulting enzyme — which they called PhotoLanZyme 1.0 (PLZ1.0) — catalyzes radical C-C bond cleavage of 1,2-diols in the presence of cerium(III) chloride and visible light. To

improve the photostability and metal binding kinetics, the team further engineered the photoenzyme by mutating tryptophans near the lanthanide binding site and introducing mutations to the

protein surface to minimize unspecific cerium binding. The final variant, PLZ1.4, could catalyze cleavage of several aromatic substituted diols in a diastereoselective manner, as well as

cleavage of aromatic lignin model compounds. Using a fusion construct of PLZ1.1 with a Lpp–OmpA sequence (previously used for surface display of artificial metalloenzymes), the team

established a whole-cell biocatalytic system for degradation of lignin model compounds in _Escherichia coli_. Finally, they demonstrated the applicability of natural lanthanide-dependent

enzymes for cerium photoredox catalysis using alcohol dehydrogenase PedH from _Pseudomonas putida_ KT2440, which requires the redox cofactor pyrroloquinoline quinone (PQQ) and a lanthanide

ion for the reaction. The enzyme was expressed and reconstituted without PQQ. In the presence of cerium(III) chloride and light, PedH could catalyze diol cleavage. This study opens new

avenues for engineering of artificial enzymes that can catalyze lanthanide-mediated photoredox reactions. This is a preview of subscription content, access via your institution ACCESS

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FAQs * Contact customer support AUTHOR INFORMATION AUTHORS AND AFFILIATIONS * Nature Communications https://www.nature.com/ncomms/ Majda Bratovič Authors * Majda Bratovič View author

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ARTICLE CITE THIS ARTICLE Bratovič, M. A cerium-dependent photoenzyme. _Nat Chem Biol_ 20, 1387 (2024). https://doi.org/10.1038/s41589-024-01767-2 Download citation * Published: 22 October

2024 * Issue Date: November 2024 * DOI: https://doi.org/10.1038/s41589-024-01767-2 SHARE THIS ARTICLE Anyone you share the following link with will be able to read this content: Get

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